(a) Field of the Invention
This invention relates to a novel therapeutic use of 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid whose generic name is etodolac. More specifically this invention relates to a method of inhibiting joint ankylosis in mammals for the treatment of arthritides.
(b) Prior Art
The active agent of this invention, 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid or a therapeutically acceptable salt thereof, is disclosed in U.S. Pat. No. 3,939,178. This active agent, hereinafter designated by its generic name etodolac, has been reported to have analgesic and anti-inflammatory properties. It has been further reported to be active in the treatment of adjuvant arthritis, a model of inflammatory arthritis sensitive to treatment with nonsteroidal anti-inflammatory drugs, in U.S. Pat. No. 4,533,551. Collagen-induced arthritis in mice is an experimental model of arthritis that lacks sensitivity to treatment with typical non-steroidal anti-inflammator drugs [Phadke K. et al.: "Evaluation of the effects of various antiarthritic drugs on type II collagen-induced mouse arthritis model", Immunopharmacology 10, 51-60 (1985)]. Collagen-induced arthritis is an experimental disease model with a number of pathological, histological, immunological, and genetic characteristics in common with rheumatoid arthritis (Trentham DE: "Collagen arthritis as a relevant model for rheumatoid arthritis: evidence pro and con," Arthritis Rheum 1982; 25: 911-916.). Collagen-induced arthritis represents an autoimmune disease, since the immunization of mice with heterologous type II collagen gives rise to an arthritogenic reaction against autologous collagen (Holmdahl R. Jansson L. Gullberg D. Forsberg PO, Rubin K and Klareskog L: "Incidence of arthritis and autoreactivity of anti-collagen antibodies after immunization of DBA/1 mice with heterologous and autologous collagen II," Clin Exp. Immunol 1985; 62:639-646.)
It has now been found unexpectedly that etodolac, either in its free acid form or in its therapeutically acceptable salt form, is useful for inhibiting joint ankylosis in mammals for the treatment of arthritides.
This finding, coupled with the fact that etodolac is a relatively safe drug, renders the method of this invention particularly useful and advantageous.